Publications

The success of Type Ia supernova (SN Ia) distance standardisation for cosmology relies on a single global linear relationship between their peak luminosity and colour, the $β$ parameter. However, there are several pieces of evidence and physical reasons to believe that this relation is not universal and may change within different subgroups, or even among individual objects. In this work, we allow $β$ to vary among subpopulations with different observed properties in the cosmological fits. Although the inferred cosmological parameters are consistent with previous studies that assume a single colour-luminosity relation, we find that the SN data favour nonuniversal distributions of $β$ when split according to SN colour and/or host-galaxy mass. For galaxy mass, we obtain a $β$-step relation in which low $β$ values occur in more massive galaxies, a trend that can be explained by differing dust reddening laws for two types of environments. For colour, we find that bluer/redder SNe Ia are consistent with a lower/larger $β$. This trend is explained with $β$ being a combination of a low intrinsic colour-luminosity relation dominant in bluer SNe and a higher extrinsic reddening relation dominant at redder colours. The host galaxy mass-step correction always provides better distance calibration, regardless of the multiple $β$ approaches, and we suggest that it may come from a difference in intrinsic colour-luminosity properties of SNe Ia in two types of environments. Additionally, we find that blue SNe in low-mass environments are better standard candles than the others.

We present an optical nebular spectrum of the nearby Type Ia supernova 2011fe, obtained 981 d after explosion. SN 2011fe exhibits little evolution since the +593 d optical spectrum, but there are several curious aspects in this new extremely late-time regime. We suggest that the persistence of the ~5800 Å feature is due to Na I D, and that a new emission feature at ~7300 Å may be [Ca II]. Also, we discuss whether the new emission feature at ~6400 Å might be [Fe I] or the high-velocity hydrogen predicted by Mazzali et al. The nebular feature at 5200 Å exhibits a linear velocity evolution of ~350 km s<sup>-1</sup> per 100 d from at least +220 to +980 d, but the line's shape also changes in this time, suggesting that line blending contributes to the evolution. At ~1000 d after explosion, flux from the SN has declined to a point where contribution from a luminous secondary could be detected. In this work, we make the first observational tests for a post-impact remnant star and constrain its temperature and luminosity to T ≳ 104K and L ≲ 10<sup>4</sup>L⊙. Additionally, we do not see any evidence for narrow H α emission in our spectrum. We conclude that observations continue to strongly exclude many single-degenerate scenarios for SN 2011fe.

We have studied the structures of the Pt(100) surface in the presence of gas-phase ethylene at room temperature. High-pressure scanning tunneling microscopy shows that the hexagonal reconstruction on the clean Pt(100) surface is preserved under 1 Torr of C2H4, which produces an ethylidyne and di-σ-bonded ethylene saturated surface. At 5 × 10–6 Torr of C2H4, coadsorbed CO from the background gases lifts the reconstruction, with the excess Pt atoms from the hexagonal surface forming islands on the surface. The chemisorption of CO from background gases in the vacuum system, in the nominally pure C2H4, is revealed by ambient-pressure X-ray photoelectron spectroscopy.

Abstract Cyclic dinucleotides (CDNs) and TLR ligands mobilize antitumor responses by NK cells and T cells, potentially serving as complementary therapies to immune checkpoint therapy. In the clinic thus far, however, CDN therapy has yielded mixed results, perhaps because it initiates responses potently, but does not provide signals to sustain activation and proliferation of activated cytotoxic lymphocytes. To improve efficacy, we combined CDNs with a half-life extended IL-2 superkine, H9-MSA. CDN/H9-MSA therapy induced dramatic long-term remissions of the most difficult-to-treat MHC I-deficient and MHC I + tumor transplant models. H9-MSA combined with CpG oligonucleotide also induced potent responses. Mechanistically, tumor elimination required CD8 T cells and not NK cells in the case of MHC I+ tumors and NK cells but not CD8 T cells in the case of MHC-deficient tumors. Furthermore, combination therapy resulted in more prolonged and more intense NK cell activation, cytotoxicity and expression of cytotoxic effector molecules in comparison to monotherapy. Remarkably, in a primary autochthonous sarcoma model that is refractory to PD-1 checkpoint therapy, the combination of CDN/H9-MSA combined with checkpoint therapy yielded long-term remissions in the majority of animals, mediated by T cells and NK cells. This novel combination therapy has potential to activate responses in tumors resistant to current therapies and prevent MHC I-loss accompanying acquired resistance of tumors to checkpoint therapy. One sentence summary Powerful immunotherapy effects mediated by the combination of innate agonists and superkine.

Isotropic and near-isotropic graphites are used as moderating material and major core components of operating nuclear fission reactors, such as the UK Advanced Gas-cooled Reactors (AGRs). As such materials are subjected to various stresses and loads in service, the deformation and fracture behaviour of nuclear graphite at operating temperatures is of critical importance to the integrity of the core. Due to experimental limitations, most mechanical tests performed to date to evaluate such properties in graphites have carried out at ambient temperatures, but these experiments can never fully describe the behaviour of graphite at realistic temperatures, i.e ., ~650°C for AGRs and ~1000°C outlet temperatures for Gen IV reactors. For reliable evaluations of the reactor core integrity, in situ at-temperature characterisation of nuclear graphites must be undertaken. In the current work, we present the first quantitative three-dimensional, under-load characterisation of the evolution of damage in these graphites by performing fracture toughness tests at temperatures up to 1000°C with simultaneous real time imaging using computed x-ray micro-tomography. In this work, a unique in situ ultrahigh temperature synchrotron radiation x-ray tomography facility that permits in situ investigations of damage evolution under load at temperatures up to 2000°C in vacuo or in a selective environment, was adopted. The experiments were undertaken at the hard x-ray micro-tomography beamline (BL 8.3.2) at the Advanced Light Source (Lawrence Berkeley National Laboratory). The material investigated was an unirradiated near-isotropic (1:1.1) moulded Gilsocarbon graphite extracted from stock AGR reactor core bricks. The filler coke particles, produced by calcination of Gilsonite, had a diameter of around 500 µm. The size of the specimens investigated in this study was similar to those irradiated surveillance specimens trepanned from the core bricks. Flexural strength tests (plain beam specimens under three-point bending) and fracture tests (beam specimen with sharp deep notch; radius ≤ 50 µm) were performed at three temperatures: room temperature (RT), 650°C and 1000°C.  A full x-ray tomography scan was performed at each step as the specimen was incrementally loaded. The tomography scans were then reconstructed in 3D to feed into LaVision software for full 3D strain and deformation measurements. With respect to strength properties, the nominal flexural strength measured at high temperature was found to be higher than at room temperature, with localised strain concentrations forming preferentially around the filler particles. For the fracture tests, the crack-tip opening displacement and the strain distribution ahead of the crack tip were analysed. Results indicated that crack-initiation fracture toughness K Ic values varied with temperature, and that the filler particles in the graphite structure served to deflect the fracture path and as such provided a means of extrinsic toughening to promote crack-growth toughness, as reflected in the rising R-curve behaviour of the material.  The relationships between the measured mechanical properties and the complex multiscale structure of the graphite will be discussed in detail.

Health in My Community:Conducting and Evaluating PhotoVoice as a Tool to Promote Environmental Health and Leadership Among Latino/a Youth Daniel Santiago Madrigal, Alicia Salvatore, Gardenia Casillas, Crystal Casillas, Irene Vera, Brenda Eskenazi, and Meredith Minkler What Is the Purpose of This Study? • Evaluate the use of PhotoVoice in an environmental health leadership program with a group of Latino adolescents from an agricultural area. What Is the Problem? • Latinos and low-income communities bear a disproportionate burden of exposure to environmental contaminants that can lead to health disparities. Residents of the Salinas community are exposed to chemicals used in pesticides because of large scale agricultural production in the area. • PhotoVoice has been used in a diverse array of communities; however, it has not been extensively tested with adolescents from agricultural communities. • Few tools exist to help adolescents learn about environmental health hazards and to prepare them to take action to create healthier environments. What Are the Findings? • Sixteen youth participated in the project and took a total of 712 photographs. The key themes that emerged from their pictures and discussions were: poor access to affordable, healthy foods; limited access to safe spaces for physical activity; ease of access to tobacco products; and poor working conditions for farmworkers. Positive themes or assets included committed individuals and community organizations working for a stronger community and plenty of open spaces in surrounding areas (see photos and summaries at www.cerch.org.com/chamacosycc). • Youth participants shared their photos and narrative summaries with members of their community at the main public library, an event at the local health department, on youth radio, and on public access television. • The youth coordinated two action projects to address the issues identified through PhotoVoice. The first was a 5k Run/Walk in collaboration with another local health organization to bring attention to the lack of safe space for physical activity and provide an opportunity for the community to come together and exercise. Over 800 community members participated in the event. For the second action project, youth members took initial steps toward bringing a recycling program to one of the local high schools. • Pre- and post- tests revealed that after the PhotoVoice project, youth participants were significantly more likely to report improvements in leadership, teamwork, and participatory behavior. No changes were observed on perceived ability to make a real difference in improving their city, or being able to work with other students on an issue that affects youth their city. Measurement timing issues may have resulted in under-estimation of changes observed. Exit interviews with participants showed more positive perceived impacts in ability to help make positive change and other areas than had the pretests and posttests. [End Page 267] • The biggest challenge of the project involved practical issues including: transportation to the meetings, conflicts with other activities that the youth members were involved in such as academics, sports, and extracurricular activities, and maintaining a supportive group environment. Who Should Care Most? • Communities and researchers who are interested in engaging youth in environmental health research and seek to strengthen their findings with perspectives from adolescent members of their communities. • Youth development programs which work with Latino youth from agricultural areas. Recommendation for Action • PhotoVoice should be used in agricultural communities interested in building environmental health leadership in Latino youth. The focus of the work with youth should be to create a program that is engaging, informative, builds leadership, and is centered on action. • New programs using this approach should anticipate and work to address common problems that may occur in areas including transportation, conflicting youth priorities, and effective group dynamics. • New programs should also attempt to include policy makers from the beginning to ensure the successful implementation of any policy- related goals that may arise from the PhotoVoice process. [End Page 268] Daniel Santiago Madrigal University of California, Berkeley, School of Public Health Alicia Salvatore Stanford University School of Medicine Gardenia Casillas University of California, Berkeley, School of Public Health Crystal Casillas Salinas, CA Irene Vera Salinas, CA Brenda Eskenazi University of California, Berkeley, School of Public Health Meredith Minkler University of California, Berkeley, School of Public Health Copyright © 2014 The Johns Hopkins University Press

Formate is a major reactive carbon species in one-carbon metabolism, where it serves as an endogenous precursor for amino acid and nucleic acid biosynthesis and a cellular source of NAD(P)H. On the other hand, aberrant elevations in cellular formate are connected to progression of serious diseases, including cancer and Alzheimer’s disease. Traditional methods for formate detection in biological environments often rely on sample destruction and/or extensive processing, resulting in a loss of spatiotemporal information. To help address these limitations, here we present the design, synthesis, and biological evaluation of a first-generation activity-based sensing system for live-cell formate imaging that relies on iridium transfer hydrogenation catalysis. Formate facilitates an aldehyde-to alcohol conversion on various fluorophore scaffolds to enable fluorescence detection of this one-carbon unit, including through a two-color ratiometric response with internal calibration. The resulting two-component probe system can detect changes in formate levels in living cells with high selectivity over potentially competing biological analytes. Moreover, this activity-based sensing system can visualize changes in endogenous formate fluxes through alterations of one-carbon pathways in cell-based models of human colon cancer, presaging the potential utility of this chemical approach to probe the continuum between one-carbon metabolism and signaling in cancer and other diseases.

ABSTRACT Progressive increases in the precision of the Hubble-constant measurement via Cepheid-calibrated Type Ia supernovae (SNe Ia) have shown a discrepancy of ∼4.4σ with the current value inferred from Planck satellite measurements of the cosmic microwave background radiation and the standard $\Lambda $cold dark matter (ΛCDM) cosmological model. This disagreement does not appear to be due to known systematic errors and may therefore be hinting at new fundamental physics. Although all of the current techniques have their own merits, further improvement in constraining the Hubble constant requires the development of as many independent methods as possible. In this work, we use SNe II as standardisable candles to obtain an independent measurement of the Hubble constant. Using seven SNe II with host-galaxy distances measured from Cepheid variables or the tip of the red giant branch, we derive H$_0= 75.8^{+5.2}_{-4.9}$ km s−1 Mpc−1 (statistical errors only). Our value favours that obtained from the conventional distance ladder (Cepheids + SNe Ia) and exhibits a difference of 8.4 km s−1 Mpc−1 from the Planck + ΛCDM value. Adding an estimate of the systematic errors (2.8 km s−1 Mpc−1) changes the ∼1.7σ discrepancy with Planck +ΛCDM to ∼1.4σ. Including the systematic errors and performing a bootstrap simulation, we confirm that the local H0 value exceeds the value from the early Universe with a confidence level of 95 per cent. As in this work, we only exchange SNe II for SNe Ia to measure extragalactic distances, we demonstrate that there is no evidence that SNe Ia are the source of the H0 tension.

Synthetic spectra generated with the parameterized supernova synthetic-spectrum code SYNOW are compared to spectra of the Type Ia SN 1994D that were obtained before the time of maximum brightness. Evidence is found for the presence of two-component Fe II and Ca II features, forming in high velocity ($\ge 20,000$ \kms) and lower velocity ($\le 16,000$ \kms) matter. Possible interpretations of these spectral splits, and implications for using early--time spectra of SNe Ia to probe the metallicity of the progenitor white dwarf and the nature of the nuclear burning front in the outer layers of the explosion, are discussed.